Substance abuse, whether by parenteral or non-parenteral means, is a well- documented risk factor for the acquisition of infection caused by the Human lmmunodeficiency Virus, type 1, [HIV-1], a fact borne out by the ever-increasing rates of infection among persons who are drug users. Among common substances of abuse, heroin and cocaine are known to have immunomodulatory effects. The major consequences of HIV-1 infection are also due to its effect on the immune system. The immunological impact of these substances in HIV-infected users have not been well characterized, furthermore, most of the data presented thus far have been obtained from parenteral drug users. Highlighting the need for a more thorough assessment of this parameter are the observed higher pre-AIDS morbidity and mortality in HIV-infected drug users, when compared to other HIV- infected groups, a circumstance-which is not readily predicted by the use of absolute CD4 counts or percentages, the current "gold standard" used for prognostic and therapeutic purposes. This suggests that, in the case of HIV-infected drug users, the absolute CD4 counts or percentages may not be a sensitive enough marker for the severity of immune dysfunction or disease progression. In addition to CD4 lymphocytes, CD8 lymphocytes have also been shown to play a substantial role in the course of HIV infection, including inhibition of HIV replication, in vitro, in naturally infected CD4 lymphocytes. Furthermore certain CD4 and CD8 subsets appear to correlate well with stage of HIV infection. The goal of this project is to develop a practical model for the clinical assessment of the severity of immune dysfunction in HIV-infected individuals who have been or are active users of heroin and/or cocaine, using CD4 and CD8+ lymphocyte subsets.The specific aims of this proposal are:1. To assemble cohorts of HIV seronegative and seropositive active and previous users of Heroin and Cocaine; HIV seronegative immunocompetent, heterosexual non-drug users; HIV seropositive heterosexual non-drug users; 2.To determine the absolute counts and percentages of the following CD4 and CD8 lymphocyte subsets in the study population using specific monoclonal antibodies: 3.To assess the immune responsiveness of CD4 and CD8 lymphocytes in the study populations, as indicated by the proliferative responses to the mitogen, Phytohemagglutinin[PHA]; 4.To correlate the numbers, function and relative proportions of said CD4 and CD8 lymphocyte subsets with clinical evidence of immune dysfunction in the cohort of HIV seronegative and seropositive Heroin and Cocaine users; 5.To utilize the data generated from this study to develop the postulated clinical model.